About XLRP and Choroideremia
X-linked retinitis pigmentosa (XLRP) is a rare inherited X-linked recessive genetic disorder, which causes progressive vision loss and blindness in boys and young men. Approximately 20,000 individuals in the US and EU have XLRP caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene.
Choroideremia is an X-linked, slowly-progressive, degenerative disease of the retina and choroid of the eye caused exclusively by mutations in the CHM gene. Approximately 10,000 individuals in the US and EU have Choroideremia, with similar prevalence rates globally.
Conventional AAV gene therapy approaches under development for XLRP, Choroideremia and other rare retinal diseases require delivery by subretinal injections.
About Wet Age-related Macular Degeneration (Wet AMD)
Wet AMD is a type of macular degeneration where abnormal blood vessels (choroidal neovascularization) grow into the macula of the retina. There are on average 200,000 new incidences of Wet AMD per year in the United States alone. Wet AMD accounts for 10% of all diagnosed cases of AMD, but it results in 90% of the legal blindness caused by all types of AMD. Most anti-VEGF therapies require repeated intravitreal injections every few months to obtain full efficacy.
4DMT Pipeline Products: 4D-125 & 4D-110
Proprietary Vector Designed for Intravitreal Injection
We have two ophthalmology product candidates that utilize our proprietary intravitreal vector for rare monogenic binding diseases: 4D-125 in development for the treatment of XLRP and 4D-110 in development for the treatment of Choroideremia. Our proprietary vector for these ophthalmological diseases is designed for intravitreal injection, potentially leading to transgene expression across the surface area of the retina, and major cell layers of the retina.
Patient Natural History Study
We have fully enrolled a natural history trial of approximately 50 patients with CHM to document the rate of visual and anatomical decline, and to identify candidates who are most likely to benefit from participation in our planned Phase 1/2 clinical trial. We expect that some of these subjects will enroll in our planned Phase 1/2 clinical trial or other future trials we may conduct.
We have an exclusive partnership in ophthalmology with Roche that includes an option for Roche to license 4D-125 in XLRP, as well as other ophthalmology product candidates we may declare, prior to pivotal trial initiation. 4D-125 is expected to enter clinical trials in mid-2020. In addition, Roche currently holds a license to 4D-110 in Choroideremia. We expect to initiate 4D-110 clinical trials in the second half of 2020.
Wet Age-related Macular Degeneration (Wet AMD)
In addition to rare ophthalmic diseases, we are also evaluating AAV gene therapy candidates for large market diseases. We have constructed product candidates in lead optimization designed to deliver various anti-VEGF transgene candidates to treat Wet AMD and other related disorders. We believe these anti-VEGF transgene candidates express proteins that have a high degree of similarity to approved anti-VEGF protein therapeutics, which we believe may increase the likelihood of technical success with these product candidates.
We are currently in lead optimization for multiple product candidates that utilize our proprietary intravitreal vector, the same as for 4D-125 and 4D-110 described above, for the treatment of Wet AMD, each of which is engineered to express a different protein to neutralize vascular endothelial growth factor (VEGF). We expect to complete lead optimization in the first half of 2020.